Capacitive affinity sensors have been used to measure the concentration of an analyte by detecting a change in capacitance as an analyte molecule moves in or out of an electric field between two electrodes of the sensor in a direct mode, for instance. The moving analyte molecules change the dielectric properties of a biochemically active layer between the two electrodes. The displacement of the solvent molecules by the analyte molecules reduces the measured capacitance between the two electrodes. The capacitance between the two electrodes changes in relation to the concentration of the analyte being measured by such a sensor, for instance. In an indirect mode, large detector molecules, such as antibodies, move in or out of the electric field between the two electrodes to change the dielectric properties of the biochemically active layer. Such capacitive affinity sensors, however, have a sensitivity limited by the amount of water displaced from the sensor surface by biomolecules.
Such sensors are described in the background of parent U.S. Pat. application Ser. No. 244,677; for BIOCHEMICAL SENSOR RESPONSIVE TO BUBBLES filed Sept. 15, 1988; to Arnold L. Newman; and assigned to the same assignee as the present invention. The background of U.S. Pat. application Ser. No. 244,677 is incorporated by reference.
U.S. Pat. No. 4,562,157 for a DIAGNOSTIC DEVICE INCORPORATING A B LIGAND; patented Dec. 31, 1985; to Christopher R. Lowe et al.; concerns a technique for covalently binding a biochemical group to a sensor surface through a mask, making possible "printed circuits for proteins". The patent states at Column 9, line 65-21, that the device of the invention need not be based on an FET. Other sensors can include transistor semiconductors, electrodes, crystals, opto-electronic devices, and fiber optic devices, for example.
FIG. 1 is from U.S. Pat. application Ser. No. 244,677 and illustrates biochemical activity of a capacitive sensor 10, which is responsive to bubbles. APS (3-aminopropyltriethoxy silane) 20 covers a layer of silicone rubber 18. APS 20 covalently binds and immobilizes a layer of an enzyme 21 to the silicone layer. APS is not necessary when the enzyme 21 is immobilized by adsorption onto the silicone layer 18. These immobilized enzyme molecules remain attached and stationary in the presence of any other biochemistry. The thickness of the layer of enzyme 20 is actually very small compared to the irregularities in the surface of the silicone rubber 18, but for clarity the thickness of the layer of enzyme 20 is exaggerated in FIG. 1. A substrate 22 to the enzyme 21 is added to the aqueous environment 19 covering the sensor surface 10. The substrate 22, in the presence of the enzyme 21, is transformed into a volatile material, for instance. The silicone rubber 18 is a surface on which the volatile material is capable of coming out of solution into the gas phase. Accordingly, bubbles 23 nucleate on the sensor surface.
The presence of nucleated bubbles at the sensor surface drastically alters the dielectric properties measured by the sensor compared to that measured in an absence of nucleated bubbles at the sensor surface. The gas bubbles 23 on the sensor surface displace molecules of the aqueous environment 19 from the sensor surface. As a result, there is a phase change at the sensor surface and within the components of the dielectric material. Specifically, liquid molecules comprising the aqueous environment 19 over the silicone rubber 18 are displaced by gas bubbles 23 when the bubbles nucleate. The gas bubbles 23 have a dielectric constant of 1-3 and the aqueous environment 19, comprising phosphate buffered saline (PBS), has a dielectric constant of over 78. This displacement of water by gas bubbles within the dielectric material drastically changes the dielectric properties of that material and thus the capacitance between the two electrodes 11 and 12.
Further details concerning the biochemistry of the capacitive sensor 10 are described in U.S. Pat. application Ser. No. 244,677; which is incorporated by reference.